Protein catabolism is a major cellular function. It contributes to cellular homeostasis through the control of the basal turnover of cell proteins as well as through the elimination of toxic peptides and abnormal proteins. In certain situations of nutrient shortage it can also participate to the production of energy. Finally, it plays a major part in the control of cell division, differentiation and apoptosis as well as in the initiation of the specific immune response. Work conducted by many laboratories have recently begun to unveil the complexity of the mechanisms for regulated protein degradation. The latter are reviewed herein.